Antisense DNA Approach to the Growth of Human Glioma Cells

Abstract

We were able to detect mRNA transcripts of transforming growth factoralpha (IFN-rα) in four of seven glioma cell lines. Transcripts of other oncogene products were not as clear as TGF-α. We then used four phosphorothioate oligonucleotides (S-oligo) complementary to the sense mRNA of erbB2, TGF-α, c-fos, and c-myc to investigate those effects on the growth of glioma cells. The antisense oligonucleotides complementary to IFN-rα and epidermal growth factor receptor (EGFR) mRNA were efficiently incorporated into glioma cells within 48 h of incubation. Exposure of human glioma cells to S-oligo against IFN-rα inhibited cell proliferation in a time- and dose-dependent fashion. These effects of the antisense IFN-rα S-oligo were significant at 3 mM, and [3H]thymidine uptake by glioma cells was inhibited by 80%. The addition of anti TGF-α antibody (50 ng/ml) enhanced these antiproliferative effects. The antisense IFN-rα S-oligo also suppressed completely the proliferation of the glioma cells throughout the extended culture period. These results clearly support a role of IFN-rα protein in the proliferation process of glioma cells, which can be blocked by means of synthetic oligonucleotides complementary to their coding exons.